Published online before print September 6, 2007

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(American Journal of Pathology. 2007;171:1381-1394.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061258

Suppression of Activation of Signal Transducer and Activator of Transcription-5B Signaling in the Vessel Wall Reduces Balloon Injury-Induced Neointima Formation

Venkatesh Kundumani-Sridharan^*, Dong Wang^*, Manjula Karpurapu^*, Zhimin Liu^*, Chunxiang Zhang, Nagadhara Dronadula^* and Gadiparthi N. Rao^*

From the Departments of Physiology^* and Surgery, University of Tennessee Health Science Center, Memphis, Tennessee

Previously, we have demonstrated that STAT-5B plays a role in thrombin-induced vascular smooth muscle cell (VSMC) growth and motility. To learn more about the role of STAT-5B in vessel wall remodeling, we examined its involvement in platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMC growth and motility and balloon injury-induced neointima formation. PDGF-BB activated STAT-5B as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. PDGF-BB induced cyclin D1 expression, CDK4 activity, and Rb protein phosphorylation, leading to VSMC growth and motility, and these responses were suppressed by the blockade of STAT-5B. Increased cyclin D1 levels, CDK4 activity, and Rb protein phosphorylation were observed in 1-week balloon-injured arteries compared with uninjured arteries, and these responses were also suppressed by adenovirus-mediated expression of dnSTAT-5B. In addition, adenovirus-mediated expression of dnSTAT-5B attenuated balloon injury-induced smooth muscle cell migration from media to intima and their proliferation in intima, resulting in reduced neointima formation. These observations indicate that STAT-5B plays an important role in PDGF-BB-induced VSMC growth and motility in vitro and balloon injury-induced neointima formation in vivo.

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